UA66339C2 - Зрізаний нейротрофічний фактор, що походить з лінії гліальних клітин (gdnf), молекула днк, яка кодує gdnf, вектор, що містить зазначену молекулу днк, клітина-хазяїн, спосіб виготовлення зрізаного gdnf, фармацевтична композиція та спосіб лікування - Google Patents
Зрізаний нейротрофічний фактор, що походить з лінії гліальних клітин (gdnf), молекула днк, яка кодує gdnf, вектор, що містить зазначену молекулу днк, клітина-хазяїн, спосіб виготовлення зрізаного gdnf, фармацевтична композиція та спосіб лікування Download PDFInfo
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Neurology (AREA)
- Molecular Biology (AREA)
- Neurosurgery (AREA)
- Toxicology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Psychology (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/535,681 US6184200B1 (en) | 1995-09-28 | 1995-09-28 | Truncated glial cell line-derived neurotrophic factor |
PCT/US1996/014915 WO1997011964A1 (en) | 1995-09-28 | 1996-09-16 | Truncated glial cell line-derived neurotrophic factor |
Publications (1)
Publication Number | Publication Date |
---|---|
UA66339C2 true UA66339C2 (uk) | 2004-05-17 |
Family
ID=24135310
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
UA98031545A UA66339C2 (uk) | 1995-09-28 | 1996-09-16 | Зрізаний нейротрофічний фактор, що походить з лінії гліальних клітин (gdnf), молекула днк, яка кодує gdnf, вектор, що містить зазначену молекулу днк, клітина-хазяїн, спосіб виготовлення зрізаного gdnf, фармацевтична композиція та спосіб лікування |
Country Status (25)
Country | Link |
---|---|
US (5) | US6184200B1 (cs) |
EP (1) | EP0920448B1 (cs) |
JP (3) | JP4153036B2 (cs) |
KR (1) | KR100334739B1 (cs) |
CN (1) | CN1283659C (cs) |
AT (1) | ATE314389T1 (cs) |
AU (1) | AU707528B2 (cs) |
CA (1) | CA2232749C (cs) |
CZ (1) | CZ297326B6 (cs) |
DE (1) | DE69635675T2 (cs) |
DK (1) | DK0920448T3 (cs) |
EA (1) | EA001204B1 (cs) |
ES (1) | ES2255713T3 (cs) |
HK (1) | HK1021823A1 (cs) |
HU (1) | HU226220B1 (cs) |
IL (6) | IL144488A0 (cs) |
MX (1) | MX9802278A (cs) |
NO (1) | NO322521B1 (cs) |
NZ (1) | NZ318697A (cs) |
SI (1) | SI0920448T1 (cs) |
SK (1) | SK288094B6 (cs) |
TW (1) | TW570926B (cs) |
UA (1) | UA66339C2 (cs) |
WO (1) | WO1997011964A1 (cs) |
ZA (1) | ZA968087B (cs) |
Families Citing this family (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6184200B1 (en) * | 1995-09-28 | 2001-02-06 | Amgen Inc. | Truncated glial cell line-derived neurotrophic factor |
US6677135B1 (en) | 1996-05-08 | 2004-01-13 | Biogen, Inc. | Ret ligand (RetL) for stimulating neutral and renal growth |
DE19816186A1 (de) * | 1998-04-14 | 1999-10-21 | Univ Muenchen L Maximilians | GDNF-kodierende DNA, Teile davon und GDNF-Varianten |
US20020055467A1 (en) * | 1998-07-06 | 2002-05-09 | Johansen Teit E. | Novel neurotrophic factors |
US6507788B1 (en) * | 1999-02-25 | 2003-01-14 | Société de Conseils de Recherches et D'Applications Scientifiques (S.C.R.A.S.) | Rational selection of putative peptides from identified nucleotide, or peptide sequences, of unknown function |
US6897061B1 (en) * | 2000-06-16 | 2005-05-24 | Spinal Cord Society | Transdifferentiation of glial cells |
US7442370B2 (en) | 2001-02-01 | 2008-10-28 | Biogen Idec Ma Inc. | Polymer conjugates of mutated neublastin |
US7276580B2 (en) | 2001-03-12 | 2007-10-02 | Biogen Idec Ma Inc. | Neurotrophic factors |
US8946151B2 (en) | 2003-02-24 | 2015-02-03 | Northern Bristol N.H.S. Trust Frenchay Hospital | Method of treating Parkinson's disease in humans by convection-enhanced infusion of glial cell-line derived neurotrophic factor to the putamen |
US7245117B1 (en) | 2004-11-01 | 2007-07-17 | Cardiomems, Inc. | Communicating with implanted wireless sensor |
US20060239966A1 (en) * | 2003-10-20 | 2006-10-26 | Tornoee Jens | In vivo gene therapy of parkinson's disease |
JP2007509109A (ja) | 2003-10-20 | 2007-04-12 | エヌエスジーン・アクティーゼルスカブ | パーキンソン病のインビボ遺伝子治療 |
AU2005277227B2 (en) | 2004-08-19 | 2011-10-06 | Biogen Ma Inc. | Refolding transforming growth factor beta family proteins |
TWI501774B (zh) | 2006-02-27 | 2015-10-01 | Biogen Idec Inc | 神經性病症之治療 |
EP2054074B8 (en) * | 2006-08-04 | 2014-11-12 | Prolong Pharmaceuticals, LLC | Modified erythropoietin |
WO2008100966A1 (en) * | 2007-02-12 | 2008-08-21 | The Research Foundation Of State University Of New York | Gdnf-derived peptides |
JP5583005B2 (ja) | 2007-05-01 | 2014-09-03 | バイオジェン・アイデック・エムエイ・インコーポレイテッド | 血管新生を増大させるための組成物および方法 |
US8446454B2 (en) * | 2007-05-21 | 2013-05-21 | Polycom, Inc. | Dynamic adaption of a continuous presence videoconferencing layout based on video content |
FI20070808A0 (fi) | 2007-10-25 | 2007-10-25 | Mart Saarma | GDNF:n silmukointivariantit ja niiden käytöt |
UA112981C2 (uk) | 2011-04-11 | 2016-11-25 | Елі Ліллі Енд Компані | Варіант людського gdnf |
US10376562B2 (en) | 2013-03-15 | 2019-08-13 | The Jackson Laboratory | Methods for promoting wound healing and hair growth comprising GDNF administration |
RU2561050C2 (ru) | 2013-08-28 | 2015-08-20 | Федеральное государственное бюджетное учреждение науки Институт биофизики клетки Российской академии наук (ИБК РАН) | Применение белка yb-1 и его фрагментов для изготовления лекарственных средств при лечении болезни альцгеймера |
AU2017357931A1 (en) | 2016-11-10 | 2019-06-20 | Keros Therapeutics, Inc. | GDNF fusion polypeptides and methods of use thereof |
JP2023515915A (ja) * | 2019-12-19 | 2023-04-17 | トランスフェルト・プラス・ソシエテ・アン・コマンディテ | 腸のニューロパチーを治療するためのグリア細胞株由来神経栄養因子(gdnf)の使用 |
TW202325850A (zh) | 2021-11-29 | 2023-07-01 | 大陸商上海瑞宏迪醫藥有限公司 | Aadc、gdnf多核苷酸及其用於治療帕金森病 |
Family Cites Families (28)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4419446A (en) | 1980-12-31 | 1983-12-06 | The United States Of America As Represented By The Department Of Health And Human Services | Recombinant DNA process utilizing a papilloma virus DNA as a vector |
US4518584A (en) | 1983-04-15 | 1985-05-21 | Cetus Corporation | Human recombinant interleukin-2 muteins |
DE3572982D1 (en) | 1984-03-06 | 1989-10-19 | Takeda Chemical Industries Ltd | Chemically modified lymphokine and production thereof |
US5106627A (en) | 1987-11-17 | 1992-04-21 | Brown University Research Foundation | Neurological therapy devices |
US5158881A (en) | 1987-11-17 | 1992-10-27 | Brown University Research Foundation | Method and system for encapsulating cells in a tubular extrudate in separate cell compartments |
US4892538A (en) | 1987-11-17 | 1990-01-09 | Brown University Research Foundation | In vivo delivery of neurotransmitters by implanted, encapsulated cells |
US5011472A (en) | 1988-09-06 | 1991-04-30 | Brown University Research Foundation | Implantable delivery system for biological factors |
CA2006596C (en) | 1988-12-22 | 2000-09-05 | Rika Ishikawa | Chemically-modified g-csf |
AU648505B2 (en) | 1989-05-19 | 1994-04-28 | Amgen, Inc. | Metalloproteinase inhibitor |
US5229500A (en) | 1989-08-30 | 1993-07-20 | Regeneron Pharmaceuticals, Inc. | Brain derived neurotrophic factor |
CA1332433C (en) | 1989-09-29 | 1994-10-11 | Robert L. Sutherland | Ski structure and binding therefor |
ATE194651T1 (de) | 1989-10-16 | 2000-07-15 | Amgen Inc | Stammzellenfaktor |
US5272071A (en) | 1989-12-22 | 1993-12-21 | Applied Research Systems Ars Holding N.V. | Method for the modification of the expression characteristics of an endogenous gene of a given cell line |
WO1991010470A1 (en) | 1990-01-08 | 1991-07-25 | Brown University Research Foundation | Devices and methods for enhanced delivery of active factors |
US5202428A (en) | 1990-06-20 | 1993-04-13 | The Salk Institute For Biological Studies | DNA encoding neurotropic growth factor |
US5252714A (en) | 1990-11-28 | 1993-10-12 | The University Of Alabama In Huntsville | Preparation and use of polyethylene glycol propionaldehyde |
GEP20002243B (en) | 1991-09-20 | 2000-09-25 | Amgen Inc | Glial Derived Neurotrophic Factor |
WO1995017203A1 (en) | 1993-12-22 | 1995-06-29 | The University Of Medicine And Dentistry Of New Jersey | Novel nucleic acid sequences isolated from glial cells |
FR2717824B1 (fr) * | 1994-03-25 | 1996-04-26 | Rhone Poulenc Rorer Sa | Virus recombinants, préparation et utilisation en thérapie génique. |
US5733875A (en) * | 1994-11-15 | 1998-03-31 | Amgen Inc. | Methods of using GDNF as a neuroprotective agent |
US5739307A (en) | 1995-08-28 | 1998-04-14 | Washington University | Polynucleotide encoding neurturin neurotrophic factor |
US5731284A (en) * | 1995-09-28 | 1998-03-24 | Amgen Inc. | Method for treating Alzheimer's disease using glial line-derived neurotrophic factor (GDNF) protein product |
US6184200B1 (en) | 1995-09-28 | 2001-02-06 | Amgen Inc. | Truncated glial cell line-derived neurotrophic factor |
US5641750A (en) * | 1995-11-29 | 1997-06-24 | Amgen Inc. | Methods for treating photoreceptors using glial cell line-derived neurotrophic factor (GDNF) protein product |
US5641749A (en) * | 1995-11-29 | 1997-06-24 | Amgen Inc. | Method for treating retinal ganglion cell injury using glial cell line-derived neurothrophic factor (GDNF) protein product |
US5929041A (en) * | 1996-02-23 | 1999-07-27 | Amgen Inc. | Method for preventing and treating sensorineural hearing loss and vestibular disorders using glial cell line-derived neurotrophic factor(GDNF) protein product |
US5837681A (en) * | 1996-02-23 | 1998-11-17 | Amgen Inc. | Method for treating sensorineural hearing loss using glial cell line-derived neurotrophic factor (GDNF) protein product |
US5741778A (en) * | 1996-03-19 | 1998-04-21 | Amgen Inc. | Method for treating Huntington's disease using glial cell line-derived neurotrophic factor (GDNF) protein product |
-
1995
- 1995-09-28 US US08/535,681 patent/US6184200B1/en not_active Expired - Lifetime
-
1996
- 1996-09-16 AT AT96931618T patent/ATE314389T1/de active
- 1996-09-16 IL IL14448896A patent/IL144488A0/xx active IP Right Grant
- 1996-09-16 SI SI9630726T patent/SI0920448T1/sl unknown
- 1996-09-16 CN CNB961972335A patent/CN1283659C/zh not_active Expired - Fee Related
- 1996-09-16 UA UA98031545A patent/UA66339C2/uk unknown
- 1996-09-16 IL IL12376196A patent/IL123761A/en not_active IP Right Cessation
- 1996-09-16 DK DK96931618T patent/DK0920448T3/da active
- 1996-09-16 NZ NZ318697A patent/NZ318697A/en not_active IP Right Cessation
- 1996-09-16 CZ CZ0088298A patent/CZ297326B6/cs not_active IP Right Cessation
- 1996-09-16 AU AU70746/96A patent/AU707528B2/en not_active Ceased
- 1996-09-16 EP EP96931618A patent/EP0920448B1/en not_active Expired - Lifetime
- 1996-09-16 ES ES96931618T patent/ES2255713T3/es not_active Expired - Lifetime
- 1996-09-16 SK SK389-98A patent/SK288094B6/sk not_active IP Right Cessation
- 1996-09-16 IL IL14401896A patent/IL144018A0/xx unknown
- 1996-09-16 DE DE69635675T patent/DE69635675T2/de not_active Expired - Lifetime
- 1996-09-16 CA CA002232749A patent/CA2232749C/en not_active Expired - Fee Related
- 1996-09-16 EA EA199800301A patent/EA001204B1/ru not_active IP Right Cessation
- 1996-09-16 WO PCT/US1996/014915 patent/WO1997011964A1/en active Application Filing
- 1996-09-16 HU HU9802262A patent/HU226220B1/hu not_active IP Right Cessation
- 1996-09-16 JP JP51349497A patent/JP4153036B2/ja not_active Expired - Fee Related
- 1996-09-16 KR KR1019980702293A patent/KR100334739B1/ko not_active IP Right Cessation
- 1996-09-26 TW TW085111819A patent/TW570926B/zh not_active IP Right Cessation
- 1996-09-26 ZA ZA968087A patent/ZA968087B/xx unknown
-
1998
- 1998-03-23 MX MX9802278A patent/MX9802278A/es active IP Right Grant
- 1998-03-30 NO NO19981430A patent/NO322521B1/no not_active IP Right Cessation
-
1999
- 1999-12-09 HK HK99105788A patent/HK1021823A1/xx not_active IP Right Cessation
-
2001
- 2001-06-26 IL IL144018A patent/IL144018A/en not_active IP Right Cessation
- 2001-07-23 IL IL144488A patent/IL144488A/en not_active IP Right Cessation
-
2004
- 2004-01-07 US US10/753,592 patent/US7390781B2/en not_active Expired - Fee Related
- 2004-05-25 US US10/853,930 patent/US20040214776A1/en not_active Abandoned
- 2004-05-26 US US10/855,820 patent/US7611865B2/en not_active Expired - Fee Related
-
2007
- 2007-09-05 JP JP2007229870A patent/JP4909843B2/ja not_active Expired - Fee Related
-
2010
- 2010-06-21 JP JP2010140665A patent/JP5241037B2/ja not_active Expired - Fee Related
-
2011
- 2011-06-23 US US13/167,419 patent/US20110251267A1/en not_active Abandoned
-
2012
- 2012-02-27 IL IL218336A patent/IL218336A0/en unknown
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